臨床研究等提出・公開システム

A Clinical Study on the Efficacy and Safety of a New Method of Fecal Microbiota Transplantation (FMT) for Treatment of Autism Spectrum Disorder (ASD)

ASD FMT Clinical Research

31

Category ASD children (n=31) 1) Gender Male 23 1) Female 8 Age (years, mean+-S.E.M.) 8.06+-0.41 5-6 10 7-8 9 1) 9-10 7 11-12 5 BMI (mean+-S.E.M.) 15.90+-0.36 Autism severity n (%) 2) Normal 1 (3.2) 3) Moderate 2 (6.5) 1) Severe 28 (90.3) 1) One subject was discontinued due to subject circumstances, leaving the number of study subjects at 30. 2) Study subjects diagnosed with ASD by pediatric neurologists or other specialists were classified using the SRS-2. 3) Among the study subjects, one was in the normal range on the SRS-2 test.

1. study design A before-and-after comparison test. 2. Selection process of study subjects 2.1 Screened children: 61 2.2 Children who did not meet the selection criteria: 30 (Reasons: age, treatment of other diseases, inability to visit hospital, difficulty in obtaining a medical certificate). 2.3 Number of study subjects during the study period At the start of treatment: 31 subjects At the end of treatment (6 weeks): 31 subjects Observation period: 30 subjects 2.4 Number of dropouts and reasons for dropouts Number of dropouts: 1 Reason for dropout: Difficulty in continuing due to guardian's circumstances.

No adverse events, even minor ones, were observed among the 30 study subjects.

The effectiveness of the new FMT method in reducing ASD and related symptoms was evaluated in 30 study subjects using the following items. Statistical processing was performed using Paired T-test or Wilcoxon signed-rank test. 1. Primary Outcome measures 1.1. SRS-2 Interpersonal Responsiveness Scale At 30 weeks after FMT, the severity of ASD showed a statistically significant decrease of approximately 29% (P<0.001). When these results are expressed as the number of people by severity, it was shown that 19 of the 28 people in the severe range (approximately 68%) and 1 person in the moderate range, a total of 20 people (approximately 69%), moved to a milder range, including 6 people who moved to the normal range, demonstrating the significant effect. The reduction effect on the severity of ASD showed different values depending on the presence or absence of gastrointestinal disorders in the subjects. That is, the reduction effects for subjects with gastrointestinal disorders (n=22) and those without gastrointestinal disorders (n=8) were statistically significantly 24% (p=0.001) and 45% (P<0.001), respectively. In the future, we plan to increase the number of cases to confirm these results and then consider developing new treatments for ASD. 1.2 SRS-2 Subscales: SCI (Social Communication and Interpersonal Interaction) and RRB (Restricted Interests and Repetitive Behaviors). The reduction effect of the new FMT method on the severity of SCI and RRB was statistically significantly 28% and 33%, respectively (both P< 0.001), similar to the reduction effect on ASD severity described above. These results showed that the new FMT method had an almost uniform effect on reducing ASD severity for the sub-scales SCI and BBR. Furthermore, the reduction in SCI severity extended almost uniformly across the four sub-scales. 2. Secondary Outcome measures 2.1 SSP (Short Sensory Profile) Sensory processing disorder is an item included in RRB (Restricted Interest and Repetitive Behavior), one of the core symptoms of ASD. For the 26 study participants (approximately 87% of the total) who exhibited sensory processing disorders, the new FMT method was evaluated for its effectiveness in reducing the severity of sensory processing disorders. The results showed a statistically significant reduction of approximately 30% (P<0.001). Furthermore, the reductions in the severity of the sub-items including sensory hypersensitivity, sensory numbness, and low response/sensory seeking were statistically significant, with reductions of approximately 28% (P<0.001), 23% (P=0.006), and 28% (P<0.001), respectively. The above results indicate that the new FMT method uniformly extends to sensory processing disorders in the core symptoms, as well as their subcategories of sensory hypersensitivity, sensory blunting, and hyporesponsiveness/sensory seeking. 2.2 Gazefinder The SRS-2 is positioned as an objective assessment method. In this study, to reconfirm that evaluations using the SRS-2 do not introduce bias, we compared the results of the SRS-2 with those of Gazefinder, which is noted for its objectivity. As a result, the severity of SCI, a primary component of the SRS-2 as a measure of sociality, showed a statistically significant positive correlation with Gazefinder's 'time spent gazing at geometric patterns' (r=0.474, P=0.01), and a statistically significant negative correlation with 'time spent gazing at human figures' (r=-0.414, P=0.03). This demonstrated that the SCI results, which hold a prominent position within the SRS-2, are objective. 2.3 GSRS (Gastrointestinal Symptom Rating Scale). Of the 30 study subjects, 22 (approximately 73% of the total) had gastrointestinal disorders before FMT and were evaluated. As a result, the new FMT method statistically significantly reduced the severity of gastrointestinal disorders, achieving a reduction rate of approximately 61% (p=0.001), which exceeded the reduction rate observed for ASD severity. 2.4 BS Scale (Bristol Stool Form Scale) Before the FMT, 60% of the study subjects had normal stools, type 3 and 4, but after the FMT, the number of ideal stools, type 4, gradually increased, and after 30 weeks, the value reached 87%. This result indicates that approximately 8 out of 12 subjects who initially had feces with characteristics outside the normal range transitioned into the normal range, achieving a reduction rate of 67%. This value is similar to the improvement rate of gastrointestinal disorders (61%) and supports the effectiveness of the new FMT in treating gastrointestinal disorders. 2.5 PHQ-4 (Patient Health Questionnaire-4) Among the 30 subjects in the study, 26 subjects with depression or anxiety symptoms were evaluated using the PHQ-4, PHQ-2, and GAD-2 to assess the effectiveness of the new FMT method in reducing these symptoms. 2.5.1 PHQ-4 The new FMT method demonstrated a statistically significant reduction in the severity of depression and anxiety symptoms. The reduction rate was approximately 50% (p<0.001), which significantly exceeded the reduction rate of ASD severity by SRS-2 (approximately 29%). 2.5.2 PHQ-2 The new FMT method showed a statistically significant reduction in the severity of depression. The reduction rate was approximately 56% (P=0.001). 2.5.3 GAD-2 The new FMT method showed a statistically significant reduction in the severity of anxiety. The reduction rate was approximately 50% (p<0.001). In summary, the results described above indicate that the effects of the novel FMT extend widely to encompass a broad range of symptoms associated with ASD, including gastrointestinal disorders, depression, and anxiety.

This study evaluated the effects of a new FMT method on ASD symptoms in 30 children using the SRS-2. The results showed a 29% reduction in ASD symptom severity, impacting a broad range of core symptoms. The effects significantly varied based on the presence of gastrointestinal disorders before FMT. In addition, effects on gastrointestinal disorders, depression, and anxiety ranged from 50% to 61%. Thus, the new FMT method notably impacts ASD and its related symptoms, which have various neurological bases.

Sept. 22, 2024

Mar. 11, 2026

https://doi.org/10.3389/fped.2026.1767346

Yes

A principal investigator shall register information of a research subject with both the informed assent obtained from the research subject and the informed consent from the legal representative by the use of the Web-registration system based on the KINTONE with the log management function. When registering a patient, the investigator shall assign an identification code for the research subject which consists of numerical symbols unrelated to personally identifiable information such as the research subject's Initials and medical record ID. The anonymized data thus obtained will be shared and analyzed by the researchers participating in this study to clarify the efficacy and safety of the new FMT method in this clinical study.

https://jrct.mhlw.go.jp/latest-detail/jRCTs031230041

Tanaka Yoshimu

Jinzenkai Medical Corporation Tanaka Medical Clinic

2-3-8, Ikuno-Nishi, Ikuno-ku, Osaka-city, Osaka, Japan

tnkzen@xa3.so-net.ne.jp

Tanaka Yoshimu

Jinzenkai Medical Corporation Tanaka Medical Clinic

2-3-8, Ikuno-Nishi, Ikuno-ku, Osaka-city, Osaka, Japan

+81-6-6711-3770

tnkzen@xa3.so-net.ne.jp

Complete

April. 18, 2023

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1. Children between the ages of 5 and 12,
regardless of gender, who have recently been
diagnosed with ASD by a board-certified pediatric
neurologist of The Japanese Society of Child
Neurology, a board-certified psychiatrist of
The Japanese Society for Psychiatry and Neurology,
a board-certified member of The Japanese Society
for Child and Adolescent Psychiatry, or a
board-certified member of Japanese Society of
Pediatric Psychiatry and Neurology.
2. Generally good physical health aside from
gastrointestinal problems.
3. Children who are able to give informed assent
to take part in the clinical study.
4. Children who are able to obtain informed
consent from their legally authorized
representatives to take part in the clinical study.

1. Currently on treatment with medicines.
2. Received antibiotics (excluding topical
antibiotics) within the last three months.
3. Received fecal microbiota transplantation
within the last 12 months.
4. Children with a single gene disorder
(Fragile X, Rett Syndrome, Joubert Syndrome,
etc. which may affect the evaluation of ASD).
5. Children with neurosurgical or neurological
diseases.
6. Currently on tube feeding.
7. Severely underweight and malnourished
less than 65% of a standard body weight.
8. Had surgery within the last 12 months or
are scheduled to have surgery within the
next six months.
9. Current participation in other clinical trials.
10. Children who are judged by a principal
investigator to be unsuitable for other reasons.

Both

Autism Spectrum Disorder

1. Administration schedule of the SHIN-1
containing solution.
The SHIN-1 containing solution is administered
rectally once a week for 6 consecutive weeks.
The efficacy will be evaluated with the results
at 30 weeks after the start of administration.
2. Contents of the SHIN-1 containing solution
to be administered each week.
The contents of the SHIN-1 containing solution
to be administered in each week from week 1 to
week 6 are as follows.
The amount of the SHIN-1 containing solution
to be used for each week from Week 1 to Week 6
is set at 3 g, 5 g, 7 g, 9 g, 11 g, and 13g,
respectively. Six different enema preparations,
each of which is prepared by adding a 100 g
of saline solution to each SHIN-1 solution
described above, are used for administration.

ASD, Autism Spectrum Disorder

D000067877

1. SRS-2
1) Changes in the severities of ASD and its core
symptoms before and after the FMT are evaluated
by SRS-2.
2) Evaluation timings are as follows: at the time
before the FMT and at 6, 10, 14, 18, and 30
weeks after the FMT.

1. Gazefinder.
A change in the ASD severity before and after
the FMT is evaluated by the gaze rates for specific
areas on the screen of Gazefinder.
Evaluation timings are as follows: at the time
before the FMT and at 30 weeks after the FMT.

2. PHQ-4.
The PHQ-4 is a questionnaire consisting of
a 2-item depression scale (PHQ-2) and a 2-item
anxiety scale (GAD-2).
Changes in the key symptoms and the signs
of depression and anxiety before and after the
FMT are evaluated by a combined assessment
of the PHQ-2 and the GAD-2 scores.
Evaluation timings are as follows: at the time
before the FMT and at 6, 10, 14, 18, and 30
weeks after the FMT.

3. GSRS.
The GSRS is a 15-item questionnaire to evaluate
gastrointestinal symptoms which include acid
reflux (2 tems), abdominal pain (3 items),
indigestion symptoms (4 items), diarrhea
(3 items), and constipation (3items).
A change in the gastrointestinal symptoms
before and after the FMT is evaluated by the
combination of the scores of these items.
Evaluation timings are as follows: at the time
before the FMT and at 6, 10, 14, 18, and 30
weeks after the FMT.

4. BS score.
The BS scores are one of the diagnostic items
for constipation or diarrhea, which are classified
into 7 categories based on the shape,
color, and hardness of stools. A change of
constipation or diarrhea before and after the FMT
is evaluated by this score.
Evaluation timings are as follows: at the time
before the FMT and at 6, 10, 14, 18, and 30
weeks after the FMT.

5. The number and frequency of adverse events.
Adverse events are evaluated at the time when
they are observed.

6. SSP (Short Sensory Profile)
Changes in the sensory symptoms (sensory
hypersensitivity, sensory numbness, and
under-responsive/sensation seeking) before and
after the implementation of FMT, are evaluated
based on the scores of the seven items of tactile
hypersensitivity, taste/smell hypersensitivity,
movement hypersensitivity, under-responsive/
sensation seeking, auditory filtering, low activity/
weakness, and visual/auditory hypersensitivity,
and their total points.
Evaluation timings are as follows: at the time before
the FMT and at 6 and 30 weeks after the FMT.

+81-3-3470-3360

April. 17, 2023

none